complexity & change in environment, biomedicine & society

50 whys to look for genes: 35. Find “missing heritability”

[G]enomic studies have had difficulty identifying causally relevant genetic variants behind variation in human traits (McCarthy et al. 2008, Couzin-Frankel 2010). Even when many genetic variants are examined together, only a small fraction of the variation in the trait is associated with—or in statistical terms, “accounted for” by—the genetic variants. This finding has led to discussions about missing heritability (e.g., Manolio et al. 2009)…

The expectation that genetic variants could account for a larger fraction of trait variation follows from ambiguous descriptions of heritability as… the “fraction of the variance of a phenotypic trait in a given population caused by (or attributable to) genetic differences” (Layzer 1974, 1259). However, the heritability of classical heritability studies (which is Layzer’s focus) has no empirical or conceptual relationship to assessing the fraction of the variation in the trait is associated with—or in statistical terms, “accounted for” by—the genetic variants (see earlier post, Heritability, a technical term, can be visualized by non-specialists). Researchers are free to search for additional genetic variants associated with a disease, but there is no missing heritability that provides a warrant for their work.